J. Exp. Med., Volume 188, Number 9, November 2, 1998 1651-1656

Interferon  Derived from CD4⁺ T Cells Is Sufficient to Mediate T Helper Cell Type 1 Development

By Adil E. Wakil,^* Zhi-En Wang,^* James C. Ryan,^§ Deborah J. Fowell,^* and Richard M. Locksley^*

From the ^* Department of Medicine and the Department of Microbiology/Immunology, and the  Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143; and the ^§ Veterans Administration Medical Center, San Francisco, California 94121

Interferon  (IFN-) has been implicated in T helper type 1 (Th1) cell development through its ability to optimize interleukin 12 (IL-12) production from macrophages and IL-12 receptor expression on activated T cells. Various systems have suggested a role for IFN- derived from the innate immune system, particularly natural killer (NK) cells, in mediating Th1 differentiation in vivo. We tested this requirement by reconstituting T cell and IFN- doubly deficient mice with wild-type CD4⁺ T cells and challenging the mice with pathogens that elicited either minimal or robust IL-12 in vivo (Leishmania major or Listeria monocytogenes, respectively). Th1 cells developed under both conditions, and this was unaffected by the presence or absence of IFN- in non-T cells. Reconstitution with IFN--deficient CD4⁺ T cells could not reestablish control over L. major, even in the presence of IFN- from the NK compartment. These data demonstrate that activated T cells can maintain responsiveness to IL-12 through elaboration of endogenous IFN- without requirement for an exogenous source of this cytokine.

T helper type 1 cells;  interferon ;  natural killer cells;  Leishmania;  Listeria

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Hayashi, T., Gong, X., Rossetto, C., Shen, C., Takabayashi, K., Redecke, V., Spiegelberg, H., Broide, D., Raz, E. (2005). Induction and Inhibition of the Th2 Phenotype Spread: Implications for Childhood Asthma. J. Immunol. 174: 5864-5873 [Abstract] [Full Text]  
• Olivier, M., Gregory, D. J., Forget, G. (2005). Subversion Mechanisms by Which Leishmania Parasites Can Escape the Host Immune Response: a Signaling Point of View. Clin. Microbiol. Rev. 18: 293-305 [Abstract] [Full Text]  
• Rothfuchs, A. G., Kreuger, M. R., Wigzell, H., Rottenberg, M. E. (2004). Macrophages, CD4+ or CD8+ Cells Are Each Sufficient for Protection against Chlamydia pneumoniae Infection through their Ability to Secrete IFN-{gamma}. J. Immunol. 172: 2407-2415 [Abstract] [Full Text]  
• Blackstock, R., Murphy, J. W. (2004). Role of Interleukin-4 in Resistance to Cryptococcus neoformans Infection. Am. J. Respir. Cell Mol. Bio. 30: 109-117 [Abstract] [Full Text]  
• Kariyone, A., Tamura, T., Kano, H., Iwakura, Y., Takeda, K., Akira, S., Takatsu, K. (2003). Immunogenicity of Peptide-25 of Ag85B in Th1 development: role of IFN-{gamma}. Int Immunol 15: 1183-1194 [Abstract] [Full Text]  
• da Silva, T. R. M., de Freitas, J. R., Silva, Q. C., Figueira, C. P., Roxo, E., Leao, S. C., de Freitas, L. A. R., Veras, P. S. T. (2002). Virulent Mycobacterium fortuitum Restricts NO Production by a Gamma Interferon-Activated J774 Cell Line and Phagosome-Lysosome Fusion. Infect. Immun. 70: 5628-5634 [Abstract] [Full Text]  
• Smeltz, R. B., Chen, J., Ehrhardt, R., Shevach, E. M. (2002). Role of IFN-{gamma} in Th1 Differentiation: IFN-{gamma} Regulates IL-18R{alpha} Expression by Preventing the Negative Effects of IL-4 and by Inducing/Maintaining IL-12 Receptor {beta}2 Expression. J. Immunol. 168: 6165-6172 [Abstract] [Full Text]  
• Mendez, S., Gurunathan, S., Kamhawi, S., Belkaid, Y., Moga, M. A., Skeiky, Y. A. W., Campos-Neto, A., Reed, S., Seder, R. A., Sacks, D. (2001). The Potency and Durability of DNA- and Protein-Based Vaccines Against Leishmania major Evaluated Using Low-Dose, Intradermal Challenge. J. Immunol. 166: 5122-5128 [Abstract] [Full Text]  
• Gurunathan, S., Stobie, L., Prussin, C., Sacks, D. L., Glaichenhaus, N., Fowell, D. J., Locksley, R. M., Chang, J. T., Wu, C.-Y., Seder, R. A. (2000). Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T Cells. J. Immunol. 165: 915-924 [Abstract] [Full Text]  
• Lacy, D. A., Wang, Z.-E., Symula, D. J., McArthur, C. J., Rubin, E. M., Frazer, K. A., Locksley, R. M. (2000). Faithful Expression of the Human 5q31 Cytokine Cluster in Transgenic Mice. J. Immunol. 164: 4569-4574 [Abstract] [Full Text]  
• Kima, P. E., Constant, S. L., Hannum, L., Colmenares, M., Lee, K. S., Haberman, A. M., Shlomchik, M. J., McMahon-Pratt, D. (2000). Internalization of Leishmania mexicana Complex Amastigotes via the Fc Receptor Is Required to Sustain Infection in Murine Cutaneous Leishmaniasis. J. Exp. Med. 191: 1063-1068 [Abstract] [Full Text]  
• Ohteki, T., Fukao, T., Suzue, K., Maki, C., Ito, M., Nakamura, M., Koyasu, S. (1999). Interleukin 12-dependent Interferon gamma  Production by CD8alpha + Lymphoid Dendritic Cells. J. Exp. Med. 189: 1981-1986 [Abstract] [Full Text]  
• Satoskar, A. R., Stamm, L. M., Zhang, X., Satoskar, A. A., Okano, M., Terhorst, C., David, J. R., Wang, B. (1999). Mice Lacking NK Cells Develop an Efficient Th1 Response and Control Cutaneous Leishmania major Infection. J. Immunol. 162: 6747-6754 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS